Typical clinical presentation of acute myocardial infarction and confusing coronary angiography: A case report and literature review of coronary embolism

Rationale: The purpose of this article is to discuss the characteristics, diagnosis, treatment, and outcomes of cases of multiple coronary embolism (CE) highly suspected to be caused by a dislodged aneurysm of the ventricular membranous septum (AVMS) thrombus. Patient concerns: A 35-year-old man was rushed to the Chest Pain Center of Taicang TCM Hospital Affiliated to Nanjing University of Chinese Medicine for sudden onset of chest pain. The patient had severe and persistent chest pain without relief, accompanied by sweating throughout the body. Diagnosis: An electrocardiogram showed ST-segment elevation in the inferior wall leads, and blood tests suggested elevated troponin I levels. The initial diagnosis was acute ST-segment elevation myocardial infarction. Emergency coronary angiography revealed complete occlusion of the first diagonal branch, thrombolysis in myocardial infarction grade 0 flow, and smooth remaining vessels. Complete occlusion of the left anterior descending artery unexpectedly occurred during interventional treatment. Postoperative cardiac ultrasonography revealed the presence of a thrombus within the AVMS and in the apical portion of the heart. The final diagnosis was a CE. Interventions: Intraoperatively, the diagonal branch occluded segment was dilated with a balloon and intracoronary administration of tirofiban and nitroglycerin. Postoperatively, antithrombotic therapy (aspirin, clopidogrel, and rivaroxaban) was administered. Outcomes: Ten days after admission, a repeat coronary angiography showed complete restoration of left anterior descending artery flow on its own, balloon dilation was again performed on the diagonal branch, and flow was restored to thrombolysis in myocardial infarction grade 1. Six months later, the intracardiac thrombus disappeared on repeat cardiac ultrasound. Lessons: AVMS is a potential source of embolism in patients with CE. CE has features that distinguish it from atherosclerosis, and a timely and correct diagnosis can help improve patient clinical outcomes.


Introduction
Acute coronary syndrome (ACS) is usually associated with coronary atherosclerosis; however, coronary embolism (CE) is a rare and unique cause of ACS. Approximately 3% of ACS cases and 4 to 13% of acute ST-segment elevation myocardial infarction cases are due to CE. [1,2] CE is exceptionally fatal with an in-hospital mortality rate of up to 36%. [3] CE is distinguished from coronary atherosclerosis in terms of treatment strategy and prognosis. The timely, accurate identification and management of CE, which involves aggressively searching for the source of the embolism, is challenging. An aneurysm of the ventricular membranous septum (AVMS) is a rare congenital malformation of the heart originating from Written informed consent was obtained from the patient for the purpose of publication.
The authors have no funding and conflicts of interest to disclose.
All data generated or analyzed during this study are included in this published article [ the membranous ventricular septum. Embolic stroke has been reported to occur in 14% of patients with an AVMS, [4] but no cases of an AVMS leading to CE have been reported. We report the first case of a patient with multiple CEs with acute inferior wall infarction as the first presentation. Postoperative cardiac ultrasound revealed the presence of an intra-AVMS thrombus in this patient, which was highly suspected to cause CE by thrombus dislodgement. Understanding the characteristics of CE, specific treatment, and identifying the source of embolism will help improve clinical outcomes in this patient population.

Case presentation
A 35-year-old Chinese man presented to our chest pain center on June 20, 2022, with "sudden onset of chest pain for 2 hours." Two hours before the visit, the patient suddenly developed severe pain in the left precordial region at rest that persisted without relief and was accompanied by generalized sweating. The patient had visited other hospitals for chest pain in June 2021, at which time a cardiac ultrasound was performed suggesting the presence of an AVMS and a negative coronary computed tomography angiography. The patient did not have any other medical history and was not using medication long-term. The patient did not have a long history of heavy smoking or alcohol abuse, a history of allergies, or any family history of hereditary disease.
On physical examination, the vital signs were as follows: body temperature, 36.4°C; blood pressure, 15.2/10 kPa; heart rate, 60 beats per min; and respiratory rate, 17 breaths per min. In addition, there were no murmurs in the auscultation areas of each heart valve, no rales in the lungs, and no edema in the limbs. Neurological examination showed no positive signs.
A chest computed tomography scan showed no obvious abnormality. An electrocardiogram suggested ST-segment elevation in the inferior wall leads (Fig. 1). The initial diagnosis was acute ST-segment elevation inferior wall infarction. The patient immediately received oral aspirin (0.3 g), ticagrelor (180 mg), and rosuvastatin (10 mg). Coronary angiography (CAG) was immediately performed. CAG showed that the right coronary artery, left main stem coronary artery, left anterior descending artery (LAD), and left circumflex artery were completely normal without any traces of atheromatous plaque, and the first diagonal branch was distally occluded with thrombolysis in myocardial infarction (TIMI) grade 0 flow ( Fig. 2A). After unsuccessful attempts to pass the occluded segment of the diagonal branch with a Runthourth NS guidewire (Terumo Corporation in Japan, with a tip hardness of 0.8g.), the occluded segment was passed through a PILOT 50 guidewire (Abbott Laboratories in the United States, with a tip hardness of 2.0g.) supported by a microcatheter, which enabled the distal end of the guidewire to repeatedly enter the distal branch in the same direction without resistance. The occluded segment was dilated repeatedly with 1.0 mm and 1.5 mm diameter balloons, and nitroglycerin, sodium nitroprusside, and tirofiban were pushed into the coronary artery several times. After a repeat CAG, no flow was detected in the distal part of the occluded segment. We delivered the microcatheter to the distal end of the occluded segment and performed negative pressure aspiration, but no blood flow was observed. When we performed CAG again, the previously normal LAD unexpectedly developed a distal occlusion (Fig. 2B). This led us to suspect that this patient may have had a CE and not coronary atherosclerosis. We immediately inserted another Runthourth NS guidewire and delivered it with difficulty through the occluded segment of the LAD to the distal end. Eventually, the flow in the distal LAD recovered to a TIMI grade of 1, and the flow in the diagonal branch remained at a TIMI grade of 0.
On the 5th postoperative day, cardiac ultrasonography revealed an AVMS with regular contour and a wide base, a sac-like structure (13 × 14 mm) protruding into the right ventricular outflow tract, with small hypoechoic sparse tissue visible inside, suggesting the possibility of thrombus (Fig. 3A). Simultaneously, the left ventricular inferior wall, posterior wall, mid-lateral wall, and entire apical region were less active, with an ejection fraction of 41%. The apical ventricular wall was relatively thin and slightly expanded outward, with multiple moderately hypoechoic attachments visible inside (the largest one was 17 mm × 12 mm) and little activity (Fig. 3B).
The patient was diagnosed with CE, an AVMS, ventricular thrombosis, and heart failure. Due to the heavy thrombus burden, rivaroxaban (10 mg/day) was added to the antiplatelet therapy (aspirin 0.1 g/ day, clopidogrel 75 mg/day). On the tenth day of admission, we performed CAG again. The angiogram showed complete normalization of the LAD occlusion; however, there was still no flow in the occluded segment of the diagonal branch (Fig. 2C). The diagonal branch was again subjected to percutaneous transluminal coronary angioplasty, and a TIMI grade 1 flow was eventually restored (Fig. 2D). No episodes of atrial fibrillation were observed on 48-hour ambulatory electrocardiogram performed during hospitalization.
After 15 days of hospitalization, the patient was discharged without incident. Six months later, the patient's repeat cardiac ultrasound showed that both the apical and intra-AVMS thrombi disappeared and that the left ventricular ejection fraction recovered to 45%. The formerly occluded segment of the coronary angiogram returned to normal. The patient refused surgical treatment for the AVMS.

CE
CE is a secondary phenomenon and is usually associated with a primary disease or etiology. Common causes include atrial fibrillation, infective endocarditis, paradoxical embolism (e.g., patent foramen ovale or atrial septal defect), iatrogenic causes (e.g., surgical material, thrombus in an interventional catheter, dislodged atherosclerotic plaque), dislodged thrombus in a wall attached to the heart, autoimmune disease, or even malignancy. There may be an overlap between the various etiologies. Embolic tissue can be a thrombus, surgical material, adipose tissue, source of infection, cancerous emboli, etc. [1,5] Defining the etiology and embolic tissue of CE facilitates the subsequent treatment and prognosis of the disease. However, notably, the underlying cause is unknown in some cases of CE.
CE usually appears on imaging as a truncated filling defect in 1 or more coronary arteries and lacks signs of coronary atherosclerosis. The most commonly affected vessel is the LAD, followed by the right coronary artery and left main stem coronary artery. [5] Some patients present with "bystander atherosclerosis," which makes the diagnosis of CE more challenging. During the intervention, the percutaneous transluminal coronary angioplasty guidewire encounters resistance through the embolic tissue that is usually greater than that of the lipid plaque formed in the coronary artery, making it more difficult to restore the blood flow to the distal end. Therefore, aspiration thrombectomy should also be considered. Pathological tissue examination of the aspirated material was performed to determine the nature and source of the embolic tissue. Postoperative anticoagulation therapy should be considered, and some patients with stent implantation will also need antiplatelet therapy. However, a consensus on treatment has not been reached because there is very little relevant data available.
Ventricular thrombosis is a common and severe complication of myocardial infarction and is an independent predictor of future cardiovascular events. [6][7][8] In general, most left ventricular thrombi form within 1 to 2 weeks after an acute event. [9] Epidemiological data show that 15% of patients with ST-segment elevation myocardial infarction and 25% of patients with anterior wall infarction present with left ventricular thrombus. [10] Patients with left ventricular thrombosis have a higher chance of suffering complications such as bleeding, renal failure, shock, and cardiac arrest than patients without left ventricular thrombosis. However, existing studies on ventricular thrombosis are largely based on classical atherosclerosis-induced infarction, and few have examined ventricular thrombosis after CE. It has not been reported whether the incidence of ventricular www.md-journal.com thrombosis after CE is different from that of atherosclerosis-induced ventricular thrombosis. Patients with CE usually have a high probability of developing other systemic embolisms, and a retrospective analysis showed that up to 15% of patients with CE had clinical evidence of stroke. [11] Therefore, to reduce the risk of a recurrent embolic event, patients should be screened for the source of embolic material and systemic embolism after surgery. The prognosis of acute myocardial infarction secondary to CE may be worse than that of myocardial infarction secondary to coronary atherosclerosis, possibly because sudden CE does not allow sufficient time for collateral circulation to develop. In addition, the prognosis of CE is significantly correlated with primary disease.

Differentiation from spontaneous coronary artery dissection (SCAD)
SCAD is another rare cause of ACS and has a similar angiographic presentation to CE; however, the 2 are distinct conditions that require differentiation. SCAD occurs frequently in women under 50 years of age and is characterized by true and false lumens caused by hematomas within the coronary mesothelium, most often in the LAD. [12,13] The disease is generally observed to heal spontaneously, so conservative treatment is preferred. The etiology may be related to fibromuscular dysplasia, pregnancy, autoimmune diseases, or mental stress. [13] CAG remains an important diagnostic modality for SCAD. However, CE can mimic the angiographic features of SCAD, making the differential diagnosis challenging. Coexisting fibromuscular dysplasia, hereditary connective tissue disease, pregnancy-related disease, and complete coronary recovery support the diagnosis of SCAD. [14,15] SCAD is uncommon in cases of non-acute onset ACS, in male patients, and in young (<25 years) or very old (>80 years) individuals. CE usually has a primary event leading to an embolic event, enabling the source of the embolism to be identified. Based on angiographic images, Yip and Saw classify SCAD into 3 types [16] ; double-lumen and long and smooth stenosis are included in the classification criteria, but these criteria do not include complete occlusion of the vessel due to SCAD. Therefore, vascular occlusions not meeting the criteria of types 1 to 3 may be classified as type 4. Both CE and SCAD (type 4) present with occlusion of the coronary arteries, whereas the rest of the vessels are essentially normal; however, truncated occlusion of multiple coronary branches is highly suggestive of CE. SCAD (type 4) is usually characterized by progressive thinning of the upstream coronary artery before the occluded segment and the presence of a double-lumen appearance in the long segment of the stenosis, a feature that can be explained by the pathological features of SCAD. SCAD (type 4) rarely presents with truncation of the coronary artery, as single-vessel changes are more common. Although the above features provide a diagnostic and differential diagnosis in most patients, there remains uncertainty in using CAG alone to distinguish SCAD (type 4) from CE. Furthermore, the use of CAG alone can leave diagnostic doubt, and intracoronary imaging is often helpful. Some patients require follow-up with CAG or coronary computed tomography angiography. Most patients with SCAD heal after 1 month, and while some patients with CE due to thrombosis may heal, the healing time is usually shorter than that in SCAD patients.

AVMS
An AVMS is a rare congenital malformation of the heart. Despite current advances in ultrasound and magnetic resonance diagnostic techniques, it is still difficult to determine the prevalence of this condition. An AVMS occurs below the septal leaflets of the tricuspid valve, and the absence of localized septal myocardium results in an aneurysm-like change that anatomically manifests as a fibrous wall sac protruding from the septal membrane into the right ventricular outflow tract. [17,18] The diagnosis is usually confirmed by echocardiography, cardiac magnetic resonance imaging, or computed tomography. In most cases, the AVMS itself is not hemodynamically significant, but the presence of local hemodynamic alterations and local ventricular wall motion abnormalities within this particular cystic structure leads to the risk of potential complications, such as rupture, thrombosis, aortic valve prolapse, tricuspid valve insufficiency, right ventricular outflow tract obstruction, endocarditis, and arrhythmias. [19,20] The presence of turbulent flow within the AVMS, which is prone to thrombus formation, promotes the development of embolic events. Some reports suggest that intra-aneurysmal thrombosis is present in 11.6% of adult patients with AVMS, [4] which is a clear independent predictor of embolic stroke. CE events due to an AVMS are rarely reported because the coronary arteries do not follow a relatively linear trajectory of the left ventricular outflow tract. After the thrombus dislodges from the left ventricle, it has a greater chance of entering the carotid artery or distal body circulation with high-velocity blood flow; therefore, there is a natural anatomical mechanism that protects against thrombotic events in the coronary arteries. In adults, if an AVMS does not spontaneously subside or shrink, surgical intervention is less likely to be required if there are no significant complications, and regular cardiac ultrasound is performed instead. Surgical repair is recommended if there are significant complications such as cerebral embolism and hemodynamic abnormalities. In the current case study, a mass found within the AVMS was suggestive of thrombosis, and anticoagulation therapy was reasonable.

Conclusion
AVMS is a potential source of embolism in patients with CE. The risk of thrombotic events in patients with an AVMS is higher than previously reported. CE has features that distinguish it from atherosclerosis and SCAD, and a timely and correct diagnosis can help improve patient clinical outcomes.